Hydrogel is widely used as a scaffolding material for tissue engineering due to its excellent cytocompatibility and potential for biofunctionalization. However, its poor mechanical property limits its further application. Fabrication of fiber-reinforced hydrogel composite scaffolds has emerged as a solution to overcome this problem. However, existing strategies usually produce nonporous composite scaffolds, where the interfiber pores are completely filled with hydrogel. This design can hinder oxygen and nutrient exchange between seeded cells and the culture medium, thereby limiting cell invasion and colonization within the scaffold. In this study, sodium alginate (SA) hydrogel was exclusively grafted onto the surface of the constituent fibers of the melt electrowritten scaffold while preserving the porous structure. The grafted hydrogel amount and pore size were precisely controlled by adjusting the SA concentration and the crosslinking ratio (SA: CaCl2). Experimental results demonstrated that the porous composite scaffolds exhibited superior swelling capacity, degradation ratio, mechanical properties, and biocompatibility. Notably, at an SA concentration of 0.5% and a crosslinking ratio of 2:1, the porous composite scaffold achieved optimal cell adhesion and viability. This study highlights the critical importance of preserving porous structures in composite scaffolds for tissue-engineering applications.
Qifan Wang,Wenjie Ye,Zhiyong Ma,Wenjia Xie,Linna Zhong,Ying Wang,Qiong Rong
Scaffolds prepared by 3D printing are increasingly used in the field of bone tissue repair. However, on traditional 3D printed bone tissue engineering scaffolds, cells can only grow on the fiber surface and form bone. We designed a scaffold with a cross-scale structure of PCL/β-TCP, which contains thick fibers with a diameter of 500 μm printed by FDM. And in the pores of the coarse fiber, the ultra-high precision fine fiber grid with a diameter of about 10 μm is filled by MEW mode. In cell experiments, cells can not only grow on the thick fiber surface of the cross-scale scaffold. At the same time, the mesh structure of fine fibers provides a bridge for cell growth, allowing cells to pass through the pores of thick fibers and grow in the pores and gradually cover the pores of the scaffold. In the osteoinduction experiment, β-TCP in the PCL/β-TCP composite provides Ca 2+ and PO 4 3− to the scaffold, which effectively promotes the osteogenic differentiation of cells on the scaffold. Compared with traditional scaffolds, the osteogenic performance of cross-scale scaffolds is greatly improved. Not only did bone form on the surface of the scaffold, but also obvious ALP expression and effective calcium precipitation appeared in the pores of the scaffold. This can effectively speed up the repair of bone defects. We believe that the 3D printed PCL/β-TCP cross-scale scaffold with high-precision fibers has great application prospects in the field of bone tissue engineering.
Secretomes from mesenchymal stem cells (MSCs) have significant therapeutic potential and could be the basis for future MSCs treatments. Innovative design of the topology of biomaterials, which mechanically regulate cell behavior and function, can tremendously improve the efficacy of stem cell therapy. However, how spatial dimension cues derived from specific topology command cell mechanotransduction to regulate the paracrine function of MSCs remains unknown. In this study, the three-dimensional (3D) fibrous constructs with box-like pores and precise strand spacing from 150 μm down to only 40 μm were manufactured using melt electrowriting (MEW), which were used to systematically investigate the spatial dimension cues-triggered mechanotransduction of adipose-derived mesenchymal stem cells (Ad-MSCs) and their impact on the paracrine and regeneration function of Ad-MSCs. The results demonstrated that spatial instructions from the 3D fibrous constructs could influence the spatial reorganization of the cytoskeleton, resulting in cell elongation and augmented immunomodulatory and angiogenic paracrine effects of Ad-MSCs, which was most pronounced at a minimum strand spacing of 40 μm. Besides, mechanical activation of the FAK-PI3K/AKT axis significantly enhanced the paracrine function of Ad-MSCs. In vivo experiments demonstrated that the Ad-MSCs trained using well-defined 3D fibrous constructs with a strand spacing of 40 μm significantly promoted skin regeneration via paracrine signals. In conclusion, this study provides a new horizon for deciphering space dimension insights into the interactional mechanisms of mechanotransduction in regulating cell function, which has inspired innovations in biomaterials for improving tissue regeneration. Statement of Significance Designing cell-scale spatial dimension cues in engineered constructs potentiates the paracrine and regenerative functions of Ad-MSCs. FAK-PI3K/AKT signaling serves as the key mechanotransduction checkpoints for spatial dimension cues triggering mechanical activation. Paracrine signals of Ad-MSCs triggered by mechanical activation promotes skin repair and regeneration via the immunomodulation and angiogenesis.
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